st1968 intravenous (weekly) in solid tumors

Conditions: Solid Tumors

Summary: st1968 is a novel camptothecin derivative which interacts with topoisomerase i-dna complex, inducing s-phase specific cytotoxicity. it is endowed with a potent antitumor activity and an increased therapeutic index with respect to the clinically used analogues (i.e.irinotecan and topotecan) in some xenograft models (ovary, colon, head \& neck, cervix). anti-tumor activity has been also noted in platinum resistant ovarian cell xenografts and in topoisomerase i mutant prostate cell lines. the acceptable toxicity profile in animals and the activity in camptothecin-resistant cell lines make st1968 a good candidate for clinical trials.

multicenter, open label, uncontrolled phase i pharmacokinetic trial to determine the maximum tolerated dose (mtd) of st1968 given intravenously (i.v.) once every week for 2 consecutive weeks every 3 weeks and the mtd of st1968 given i.v. once every 3 weeks. a starting dose of 1.5mg/m2 given as a flat dose of 2.5mg is defined, given once on day 1, day 8 every 21 days (d1, d8 q21d schedule), over 2 h. starting dose for the day 1 every 21 days (d1 q21d schedule) has to be determined from the mtd of d1, d8 q21d schedule. plasma, urine pharmacokinetics in all patients (minimum of 3 pts for each cohort) during the first cycle of treatment and in at least 6 patients at the recommended dose (rd). during the study any hints of anti-tumor activity will also be evaluated by recist criteria.

Eligibility criteria:
inclusion criteria: * histological/cytological diagnosis of solid tumors for which therapy of proven efficacy does not exist. * preferably measurable disease * ecog performance status ≤ 1. * age ≥ 18 years. * ongoing toxicity associated with prior anticancer therapy ≤ grade 1 (nci-ctcae v3.0). * maximum of 2 prior chemotherapy lines for advanced disease (not including neoadjuvant or adjuvant chemotherapy) * adequate hematological, liver and renal function * hemoglobin ≥ 9 g/dl; anc ≥ 1.5 x 109/l; platelets ≥ 100 x 109/l; * serum bilirubin ≤ upper normal limit (unl). alt, ast ≤ unl but ≤ 2.5 x unl in case of liver metastases; alkaline phosphatase (liver isoenzyme fraction) ≤ unl or ≤ 1.5xuln in case of liver metastases; albumin within normal limits; * creatinine ≤1.5 mg/dl or calculated creatinine clearance ≥ 60 ml/min. * life expectancy of at least 3 months * capacity of understanding the nature of the trial and giving written informed consent. exclusion criteria: * less than 4 weeks since last chemotherapy, radiotherapy or prior investigational therapy. less than 2 weeks since last hormone or immunotherapy or signal transduction therapy. * active infection. * presence of cirrhosis or chronic hepatitis * presence of serious cardiac (congestive heart failure, angina pectoris, myocardial infarction within one year prior to study entry, uncontrolled hypertension or arrhythmia), neurological or psychiatric disorder. * presence of uncontrolled intercurrent illness or any condition which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study. * symptomatic brain metastases (this does not include primary brain tumors) or leptomeningeal disease. * pregnancy or lactation or unwillingness to use adequate method of birth control

Keywords: st1968 camptothecin solid tumors topoisomerase i